期刊
HYPERTENSION RESEARCH
卷 41, 期 9, 页码 679-690出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41440-018-0073-x
关键词
-
资金
- National Institutes of Health [HL-57853, HL-73287, DK67620]
This study tested the hypothesis that selective ablation of transient receptor potential vanilloid type 1 (TRPV1)-positive nerve fibers by intrathecal injection of resiniferatoxin (RTX) enhances renal sympathoexcitatory responses and salt sensitivity. Intrathecal injection of RTX (1.8 mu g/kg) to the levels of lower thoracic and upper lumbar spinal cord (T8-L3) increased mean arterial pressure (MAP) in rats fed a normal (NS, 1% NaCl) or high-sodium (HS, 8% NaCl) diet for 4 weeks compared to vehicle-treated rats (NS: 121 +/- 2 vs. 111 +/- 2; HS: 154 +/- 2 vs. 134 +/- 2 mm Hg, both P < 0.05), with a greater increase in HS compared to NS rats (9 +/- 1% vs. 15 +/- 1%, P < 0.05). TRPV1 contents were decreased in T8-L3 segments of spinal dorsal horn but not in corresponding dorsal root ganglia and the kidney following RTX treatment (P < 0.05). Selective activation of GABA-A receptors with intrathecal T8-L3 segment-injection of muscimol (3 nmol/kg) decreased renal sympathetic nerve activity and increased urinary excretion in both NS and HS rats, with a greater effect in RTX-treated compared to vehicle-treated rats (P < 0.05). Chronic activation of GABA-A receptors with muscimol (50 mg/kg/day x 2, p.o.) abolished RTX treatment-induced pressor effects in NS and HS rats. GAD65/67, a GABA synthetase, in the spinal cord was downregulated and tyrosine hydroxylase in the kidney upregulated in NS or HS rats treated with RTX (P < 0.05). Thus, selective ablation of TRPV1-positive central terminals of sensory neurons plays a prohypertensive role possibly via inhibition of spinal GABA system especially with HS intake, suggesting that activation of TRPV1 in central terminals of sensory neurons may convey an antihypertensive effect.
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